Overview

Myocet + Cyclophosphamide + Metformin Vs Myocet + Cyclophosphamide in 1st Line Treatment of HER2 Neg. Metastatic Breast Cancer Patients

Status:
Completed
Trial end date:
2015-05-01
Target enrollment:
0
Participant gender:
Female
Summary
This is a phase II comparative randomized clinical trial. Eligible patients will be randomized (1:1) to: Arm A: Myocet plus Cyclofosfamide plus Metformin Arm B: Myocet plus Cyclofosfamide Statistical Considerations: In this randomized phase II study, the sample size was calculated basing on the primary end-point (PFS) and assuming an error α = 10% (2-tailed) with a power of 80%. To find an advantage of 4 months of median time to progression (6 months in the control arm B and 10 months in the experimental arm A) will be recruited 112 patients (98 events) for a period of 24 months and will be considered further 12-month of follow-up. The primary analysis of the study will be conducted in accordance with the "intention to treat" principle, the secondary analysis will be conducted in the "per protocol" population.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Treatments:
Cyclophosphamide
Doxorubicin
Metformin
Criteria
Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed breast cancer

2. Metastatic disease

3. HER2 negative disease, as measured by IHC or FISH

4. Non endocrine responsive disease (negative hormonal status or failure of endocrine
therapy for MBC)

5. Patients with measurable and/or non-measurable disease according to RECIST Criteria
(Version 1.1)

6. Homa Index calculated according to Matthews' formula

7. Prior endocrine therapy is allowed, in the adjuvant and/or metastatic setting

8. Prior chemotherapy is allowed, only in adjuvant setting, provided it is terminated at
least 12 months before study entry. Adjuvant anthracyclines are allowed if prior
cumulative dose does not exceed 360 mg/m2 in case of epirubicin and 280 mg/m2 in case
of doxorubicin. Adjuvant taxanes are allowed.

9. Age 18-75 years

10. Life expectancy of greater than 3 months

11. ECOG performance status <2

12. Patients must have normal organ and marrow function:

- leukocytes >=3,000/μL

- absolute neutrophil count >=1,500/μL

- platelets >=100,000/μL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal

- creatinine within normal institutional limits

13. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)>= 50%

14. The effects of liposomal doxorubicin on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason and because anthracyclines as well as
other therapeutic agents used in this trial are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration
of study participation. All women of childbearing potential must have a negative serum
or urine pregnancy test within 72 hours prior to the start of study medication. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.

15. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Known diabetes (type 1 or 2)

2. Currently on metformin, sulfonylureas, thiazolidenediones or insulin for any reason
(these drugs alter insulin levels)

3. Current or previous congestive heart failure, renal failure or liver failure; history
of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day

4. Creatinine above upper limit of normal for institution, AST above 1.5 times upper
limit or normal for institution (to reduce risk of lactic acidosis)

5. Hypersensitivity or allergy to metformin

6. Participation in another clinical trial with any investigational agents within 30 days
prior to study screening

7. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events

8. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Myocet or other agents used in the study

9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.